TY - JOUR T1 - Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use. JF - Nature Genetics Y1 - 2019 A1 - Liu, Mengzhen A1 - Jiang, Yu A1 - Wedow, Robbee A1 - Li, Yue A1 - Brazel, David M A1 - Chen, Fang A1 - Datta, Gargi A1 - Davila-Velderrain, Jose A1 - McGuire, Daniel A1 - Tian, Chao A1 - Zhan, Xiaowei A1 - Choquet, Hélène A1 - Docherty, Anna R A1 - Jessica Faul A1 - Foerster, Johanna R A1 - Fritsche, Lars G A1 - Gabrielsen, Maiken Elvestad A1 - Gordon, Scott D A1 - Jeffrey Haessler A1 - Jouke-Jan Hottenga A1 - Huang, Hongyan A1 - Jang, Seon-Kyeong A1 - Philip R Jansen A1 - Ling, Yueh A1 - Mägi, Reedik A1 - Matoba, Nana A1 - McMahon, George A1 - Mulas, Antonella A1 - Orrù, Valeria A1 - Palviainen, Teemu A1 - Anita Pandit A1 - Reginsson, Gunnar W A1 - Skogholt, Anne Heidi A1 - Smith, Jennifer A A1 - Taylor, Amy E A1 - Turman, Constance A1 - Gonneke Willemsen A1 - Young, Hannah A1 - Young, Kendra A A1 - Zajac, Gregory J M A1 - Zhao, Wei A1 - Zhou, Wei A1 - Bjornsdottir, Gyda A1 - Boardman, Jason D A1 - Boehnke, Michael A1 - Dorret I Boomsma A1 - Chen, Chu A1 - Francesco Cucca A1 - Davies, Gareth E A1 - Charles B Eaton A1 - Ehringer, Marissa A A1 - Tõnu Esko A1 - Fiorillo, Edoardo A1 - Gillespie, Nathan A A1 - Gudbjartsson, Daniel F A1 - Haller, Toomas A1 - Kathleen Mullan Harris A1 - Andrew C Heath A1 - Hewitt, John K A1 - Hickie, Ian B A1 - Hokanson, John E A1 - Hopfer, Christian J A1 - Hunter, David J A1 - Iacono, William G A1 - Johnson, Eric O A1 - Kamatani, Yoichiro A1 - Sharon L R Kardia A1 - Matthew C Keller A1 - Kellis, Manolis A1 - Charles Kooperberg A1 - Kraft, Peter A1 - Krauter, Kenneth S A1 - Laakso, Markku A1 - Penelope A Lind A1 - Loukola, Anu A1 - Lutz, Sharon M A1 - Pamela A F Madden A1 - Nicholas G Martin A1 - McGue, Matt A1 - Matthew B McQueen A1 - Sarah E Medland A1 - Andres Metspalu A1 - Mohlke, Karen L A1 - Nielsen, Jonas B A1 - Okada, Yukinori A1 - Peters, Ulrike A1 - Tinca J Polderman A1 - Posthuma, Danielle A1 - Reiner, Alexander P A1 - Rice, John P A1 - Rimm, Eric A1 - Rose, Richard J A1 - Runarsdottir, Valgerdur A1 - Stallings, Michael C A1 - Stančáková, Alena A1 - Stefansson, Hreinn A1 - Thai, Khanh K A1 - Hilary A Tindle A1 - Tyrfingsson, Thorarinn A1 - Wall, Tamara L A1 - David R Weir A1 - Weisner, Constance A1 - Whitfield, John B A1 - Winsvold, Bendik Slagsvold A1 - Yin, Jie A1 - Zuccolo, Luisa A1 - Laura Bierut A1 - Hveem, Kristian A1 - Lee, James J A1 - Munafò, Marcus R A1 - Saccone, Nancy L A1 - Willer, Cristen J A1 - Marilyn C Cornelis A1 - David, Sean P A1 - Hinds, David A A1 - Jorgenson, Eric A1 - Kaprio, Jaakko A1 - Stitzel, Jerry A A1 - Stefansson, Kari A1 - Thorgeirsson, Thorgeir E A1 - Gonçalo R Abecasis A1 - Liu, Dajiang J A1 - Scott Vrieze KW - Alcohol Drinking KW - Female KW - Genetic Variation KW - Genome-Wide Association Study KW - Humans KW - Male KW - Middle Aged KW - Phenotype KW - Risk KW - Smoking KW - Tobacco KW - Tobacco Use Disorder AB -

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders. They are heritable and etiologically related behaviors that have been resistant to gene discovery efforts. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures.

VL - 51 IS - 2 ER - TY - JOUR T1 - Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence JF - Nature Genetics Y1 - 2018 A1 - Savage, Jeanne E. A1 - Philip R Jansen A1 - Stringer, Sven A1 - Watanabe, Kyoko A1 - Bryois, Julien A1 - Christiaan de Leeuw A1 - Nagel, Mats A1 - Awasthi, Swapnil A1 - Barr, Peter B. A1 - Coleman, Jonathan R. I. A1 - Grasby, Katrina L. A1 - Anke R Hammerschlag A1 - Kaminski, Jakob A. A1 - Karlsson, Robert A1 - Krapohl, Eva A1 - Lam, Max A1 - Nygaard, Marianne A1 - Chandra A Reynolds A1 - Joey W Trampush A1 - Young, Hannah A1 - Zabaneh, Delilah A1 - Hägg, Sara A1 - Narelle K Hansell A1 - Ida Karlsson A1 - Linnarsson, Sten A1 - Grant W Montgomery A1 - Muñoz-Manchado, Ana B. A1 - Quinlan, Erin B. A1 - Schumann, Gunter A1 - Skene, Nathan G. A1 - Webb, Bradley T. A1 - White, Tonya A1 - Dan E Arking A1 - Avramopoulos, Dimitrios A1 - Robert M Bilder A1 - Bitsios, Panos A1 - Katherine E Burdick A1 - Tyrone D. Cannon A1 - Chiba-Falek, Ornit A1 - Christoforou, Andrea A1 - Elizabeth T. Cirulli A1 - Congdon, Eliza A1 - Corvin, Aiden A1 - Gail Davies A1 - Ian J Deary A1 - DeRosse, Pamela A1 - Dickinson, Dwight A1 - Djurovic, Srdjan A1 - Donohoe, Gary A1 - Conley, Emily Drabant A1 - Johan G Eriksson A1 - Espeseth, Thomas A1 - Nelson A. Freimer A1 - Giakoumaki, Stella A1 - Giegling, Ina A1 - Gill, Michael A1 - David C. Glahn A1 - Ahmad R Hariri A1 - Hatzimanolis, Alex A1 - Matthew C Keller A1 - Knowles, Emma A1 - Koltai, Deborah A1 - Konte, Bettina A1 - Lahti, Jari A1 - Stephanie Le Hellard A1 - Lencz, Todd A1 - David C Liewald A1 - London, Edythe A1 - Astri J Lundervold A1 - Anil K. Malhotra A1 - Melle, Ingrid A1 - Morris, Derek A1 - Anna C Need A1 - William E R Ollier A1 - Aarno Palotie A1 - Payton, Antony A1 - Pendleton, Neil A1 - Russell A Poldrack A1 - Katri Räikkönen A1 - Reinvang, Ivar A1 - Roussos, Panos A1 - Rujescu, Dan A1 - Fred W Sabb A1 - Matthew A Scult A1 - Smeland, Olav B. A1 - Smyrnis, Nikolaos A1 - John M Starr A1 - Vidar M Steen A1 - Nikos C Stefanis A1 - Richard E Straub A1 - Sundet, Kjetil A1 - Henning Tiemeier A1 - Aristotle N Voineskos A1 - Daniel R Weinberger A1 - Elisabeth Widen A1 - Yu, Jin A1 - Gonçalo R Abecasis A1 - Andreassen, Ole A. A1 - Breen, Gerome A1 - Christiansen, Lene A1 - Debrabant, Birgit A1 - Danielle M. Dick A1 - Heinz, Andreas A1 - Hjerling-Leffler, Jens A1 - Mohammed Arfan Ikram A1 - Kendler, Kenneth S. A1 - Nicholas G Martin A1 - Sarah E Medland A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Tinca J Polderman A1 - Ripke, Stephan A1 - van der Sluis, Sophie A1 - Patrick F. Sullivan A1 - Scott Vrieze A1 - Margaret J Wright A1 - Posthuma, Danielle KW - Genome-Wide Association Study KW - Intelligence KW - Meta-analyses AB - Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders. VL - 50 UR - http://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdfhttp://www.nature.com/articles/s41588-018-0152-6http://www.nature.com/articles/s41588-018-0152-6.pdf IS - 7 JO - Nat Genet ER - TY - JOUR T1 - Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. JF - Nat Genet Y1 - 2018 A1 - Turcot, Valérie A1 - Lu, Yingchang A1 - Highland, Heather M A1 - Schurmann, Claudia A1 - Justice, Anne E A1 - Fine, Rebecca S A1 - Bradfield, Jonathan P A1 - Tõnu Esko A1 - Giri, Ayush A1 - Graff, Mariaelisa A1 - Guo, Xiuqing A1 - Hendricks, Audrey E A1 - Karaderi, Tugce A1 - Lempradl, Adelheid A1 - Locke, Adam E A1 - Mahajan, Anubha A1 - Marouli, Eirini A1 - Sivapalaratnam, Suthesh A1 - Young, Kristin L A1 - Alfred, Tamuno A1 - Feitosa, Mary F A1 - Masca, Nicholas G D A1 - Alisa Manning A1 - Medina-Gomez, Carolina A1 - Mudgal, Poorva A1 - Ng, Maggie C Y A1 - Reiner, Alex P A1 - Vedantam, Sailaja A1 - Willems, Sara M A1 - Thomas W Winkler A1 - Gonçalo R Abecasis A1 - Aben, Katja K A1 - Alam, Dewan S A1 - Alharthi, Sameer E A1 - Matthew A. Allison A1 - Amouyel, Philippe A1 - Asselbergs, Folkert W A1 - Auer, Paul L A1 - Balkau, Beverley A1 - Bang, Lia E A1 - Barroso, Inês A1 - Bastarache, Lisa A1 - Benn, Marianne A1 - Bergmann, Sven A1 - Bielak, Lawrence F A1 - Blüher, Matthias A1 - Boehnke, Michael A1 - Boeing, Heiner A1 - Boerwinkle, Eric A1 - Böger, Carsten A A1 - Bork-Jensen, Jette A1 - Bots, Michiel L A1 - Erwin P Bottinger A1 - Bowden, Donald W A1 - Brandslund, Ivan A1 - Breen, Gerome A1 - Brilliant, Murray H A1 - Broer, Linda A1 - Brumat, Marco A1 - Burt, Amber A A1 - Adam S Butterworth A1 - Campbell, Peter T A1 - Cappellani, Stefania A1 - Carey, David J A1 - Catamo, Eulalia A1 - Caulfield, Mark J A1 - Chambers, John C A1 - Daniel I Chasman A1 - Yii-Der I Chen A1 - Chowdhury, Rajiv A1 - Cramer Christensen A1 - Chu, Audrey Y A1 - Cocca, Massimiliano A1 - Collins, Francis S A1 - Cook, James P A1 - Corley, Janie A1 - Jordi Corominas Galbany A1 - Cox, Amanda J A1 - Crosslin, David S A1 - Cuellar-Partida, Gabriel A1 - D'Eustacchio, Angela A1 - Danesh, John A1 - Gail Davies A1 - Bakker, Paul I W A1 - Groot, Mark C H A1 - Mutsert, Renée A1 - Ian J Deary A1 - George Dedoussis A1 - Ellen W Demerath A1 - Heijer, Martin A1 - Anneke I den Hollander A1 - Hester M den Ruijter A1 - Joe G Dennis A1 - Denny, Josh C A1 - Angelantonio, Emanuele A1 - Drenos, Fotios A1 - Du, Mengmeng A1 - Dubé, Marie-Pierre A1 - Dunning, Alison M A1 - Easton, Douglas F A1 - Edwards, Todd L A1 - Ellinghaus, David A1 - Ellinor, Patrick T A1 - Elliott, Paul A1 - Evangelou, Evangelos A1 - Farmaki, Aliki-Eleni A1 - Farooqi, I Sadaf A1 - Jessica Faul A1 - Fauser, Sascha A1 - Feng, Shuang A1 - Ferrannini, Ele A1 - Ferrières, Jean A1 - Florez, Jose C A1 - Ford, Ian A1 - Myriam Fornage A1 - Franco, Oscar H A1 - Franke, Andre A1 - Franks, Paul W A1 - Friedrich, Nele A1 - Frikke-Schmidt, Ruth A1 - Galesloot, Tessel E A1 - Gan, Wei A1 - Gandin, Ilaria A1 - Paolo P. Gasparini A1 - Gibson, Jane A1 - Giedraitis, Vilmantas A1 - Gjesing, Anette P A1 - Gordon-Larsen, Penny A1 - Gorski, Mathias A1 - Hans-Jörgen Grabe A1 - Grant, Struan F A A1 - Grarup, Niels A1 - Griffiths, Helen L A1 - Grove, Megan L A1 - Gudnason, Vilmundur A1 - Gustafsson, Stefan A1 - Jeffrey Haessler A1 - Hakonarson, Hakon A1 - Anke R Hammerschlag A1 - Hansen, Torben A1 - Tamara B Harris A1 - Andrew T Hattersley A1 - Have, Christian T A1 - Caroline Hayward A1 - He, Liang A1 - Heard-Costa, Nancy L A1 - Andrew C Heath A1 - Iris M Heid A1 - Helgeland, Øyvind A1 - Hernesniemi, Jussi A1 - Hewitt, Alex W A1 - Oddgeir L Holmen A1 - Hovingh, G Kees A1 - Howson, Joanna M M A1 - Hu, Yao A1 - Huang, Paul L A1 - Huffman, Jennifer E A1 - Mohammed Arfan Ikram A1 - Ingelsson, Erik A1 - Jackson, Anne U A1 - Jansson, Jan-Håkan A1 - Jarvik, Gail P A1 - Jensen, Gorm B A1 - Jia, Yucheng A1 - Johansson, Stefan A1 - Jørgensen, Marit E A1 - Jørgensen, Torben A1 - Jukema, J Wouter A1 - Kahali, Bratati A1 - Kahn, René S A1 - Kähönen, Mika A1 - Kamstrup, Pia R A1 - Kanoni, Stavroula A1 - Kaprio, Jaakko A1 - Karaleftheri, Maria A1 - Sharon L R Kardia A1 - Karpe, Fredrik A1 - Kathiresan, Sekar A1 - Kee, Frank A1 - Lambertus A Kiemeney A1 - Eric S Kim A1 - Kitajima, Hidetoshi A1 - Komulainen, Pirjo A1 - Kooner, Jaspal S A1 - Charles Kooperberg A1 - Korhonen, Tellervo A1 - Kovacs, Peter A1 - Kuivaniemi, Helena A1 - Kutalik, Zoltán A1 - Kuulasmaa, Kari A1 - Kuusisto, Johanna A1 - Laakso, Markku A1 - Lakka, Timo A A1 - Lamparter, David A1 - Lange, Ethan M A1 - Leslie A Lange A1 - Langenberg, Claudia A1 - Eric B Larson A1 - Lee, Nanette R A1 - Lehtimäki, Terho A1 - Lewis, Cora E A1 - Li, Huaixing A1 - Li, Jin A1 - Li-Gao, Ruifang A1 - Lin, Honghuang A1 - Lin, Keng-Hung A1 - Lin, Li-An A1 - Lin, Xu A1 - Lars Lind A1 - Lindström, Jaana A1 - Linneberg, Allan A1 - Liu, Ching-Ti A1 - Liu, Dajiang J A1 - Yongmei Liu A1 - Ken Sin Lo A1 - Lophatananon, Artitaya A1 - Lotery, Andrew J A1 - Loukola, Anu A1 - Luan, Jian'an A1 - Lubitz, Steven A A1 - Lyytikäinen, Leo-Pekka A1 - Männistö, Satu A1 - Marenne, Gaëlle A1 - Mazul, Angela L A1 - McCarthy, Mark I A1 - McKean-Cowdin, Roberta A1 - Sarah E Medland A1 - Meidtner, Karina A1 - Lili Milani A1 - Mistry, Vanisha A1 - Mitchell, Paul A1 - Mohlke, Karen L A1 - Moilanen, Leena A1 - Moitry, Marie A1 - Grant W Montgomery A1 - Dennis O Mook-Kanamori A1 - Moore, Carmel A1 - Mori, Trevor A A1 - Morris, Andrew D A1 - Morris, Andrew P A1 - Müller-Nurasyid, Martina A1 - Munroe, Patricia B A1 - Michael A Nalls A1 - Narisu, Narisu A1 - Nelson, Christopher P A1 - Neville, Matt A1 - Sune Fallgaard Nielsen A1 - Nikus, Kjell A1 - Njølstad, Pål R A1 - Børge G Nordestgaard A1 - Nyholt, Dale R A1 - Jeff O'Connell A1 - O'Donoghue, Michelle L A1 - Ophoff, Roel A A1 - Owen, Katharine R A1 - Packard, Chris J A1 - Padmanabhan, Sandosh A1 - Palmer, Colin N A A1 - Palmer, Nicholette D A1 - Pasterkamp, Gerard A1 - Patel, Aniruddh P A1 - Pattie, Alison A1 - Pedersen, Oluf A1 - Peissig, Peggy L A1 - Peloso, Gina M A1 - Pennell, Craig E A1 - Markus Perola A1 - Perry, James A A1 - Perry, John R B A1 - Pers, Tune H A1 - Person, Thomas N A1 - Peters, Annette A1 - Petersen, Eva R B A1 - Peyser, Patricia A A1 - Pirie, Ailith A1 - Polasek, Ozren A1 - Tinca J Polderman A1 - Puolijoki, Hannu A1 - Olli T Raitakari A1 - Rasheed, Asif A1 - Rauramaa, Rainer A1 - Reilly, Dermot F A1 - Renstrom, Frida A1 - Rheinberger, Myriam A1 - Ridker, Paul M A1 - Rioux, John D A1 - Rivas, Manuel A A1 - Roberts, David J A1 - Neil R Robertson A1 - Robino, Antonietta A1 - Rolandsson, Olov A1 - Rudan, Igor A1 - Ruth, Katherine S A1 - Saleheen, Danish A1 - Veikko Salomaa A1 - Nilesh J Samani A1 - Sapkota, Yadav A1 - Sattar, Naveed A1 - Schoen, Robert E A1 - Schreiner, Pamela J A1 - Schulze, Matthias B A1 - Scott, Robert A A1 - Segura-Lepe, Marcelo P A1 - Svati H Shah A1 - Sheu, Wayne H-H A1 - Sim, Xueling A1 - Slater, Andrew J A1 - Small, Kerrin S A1 - Albert Vernon Smith A1 - Southam, Lorraine A1 - Timothy Spector A1 - Elizabeth K Speliotes A1 - John M Starr A1 - Stefansson, Kari A1 - Steinthorsdottir, Valgerdur A1 - Kathleen E Stirrups A1 - Strauch, Konstantin A1 - Heather M Stringham A1 - Stumvoll, Michael A1 - Sun, Liang A1 - Surendran, Praveen A1 - Swift, Amy J A1 - Tada, Hayato A1 - Tansey, Katherine E A1 - Tardif, Jean-Claude A1 - Kent D Taylor A1 - Teumer, Alexander A1 - Thompson, Deborah J A1 - Thorleifsson, Gudmar A1 - Thorsteinsdottir, Unnur A1 - Thuesen, Betina H A1 - Tönjes, Anke A1 - Tromp, Gerard A1 - Trompet, Stella A1 - Tsafantakis, Emmanouil A1 - Tuomilehto, Jaakko A1 - Tybjaerg-Hansen, Anne A1 - Tyrer, Jonathan P A1 - Uher, Rudolf A1 - André G Uitterlinden A1 - Uusitupa, Matti A1 - Laan, Sander W A1 - Duijn, Cornelia M A1 - Leeuwen, Nienke A1 - van Setten, Jessica A1 - Vanhala, Mauno A1 - Varbo, Anette A1 - Varga, Tibor V A1 - Varma, Rohit A1 - Digna R Velez Edwards A1 - Vermeulen, Sita H A1 - Veronesi, Giovanni A1 - Vestergaard, Henrik A1 - Vitart, Veronique A1 - Vogt, Thomas F A1 - Völker, Uwe A1 - Vuckovic, Dragana A1 - Wagenknecht, Lynne E A1 - Walker, Mark A1 - Wallentin, Lars A1 - Wang, Feijie A1 - Wang, Carol A A1 - Wang, Shuai A1 - Wang, Yiqin A1 - Erin B Ware A1 - Wareham, Nicholas J A1 - Warren, Helen R A1 - Dawn M Waterworth A1 - Wessel, Jennifer A1 - White, Harvey D A1 - Willer, Cristen J A1 - Wilson, James G A1 - Daniel Witte A1 - Andrew R Wood A1 - Wu, Ying A1 - Yaghootkar, Hanieh A1 - Yao, Jie A1 - Yao, Pang A1 - Laura M Yerges-Armstrong A1 - Young, Robin A1 - Zeggini, Eleftheria A1 - Zhan, Xiaowei A1 - Zhang, Weihua A1 - Wei Zhao A1 - Zhou, Wei A1 - Krina T Zondervan A1 - Rotter, Jerome I A1 - Pospisilik, John A A1 - Fernando Rivadeneira A1 - Ingrid B Borecki A1 - Deloukas, Panos A1 - Timothy M Frayling A1 - Lettre, Guillaume A1 - Kari E North A1 - Lindgren, Cecilia M A1 - Joel N Hirschhron A1 - Ruth J F Loos AB -

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

VL - 50 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/29273807?dopt=Abstract ER - TY - JOUR T1 - Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. JF - Nature Communications Y1 - 2017 A1 - Joshi, Peter K A1 - Nicola Pirastu A1 - Kentistou, Katherine A A1 - Fischer, Krista A1 - Edith Hofer A1 - Schraut, Katharina E A1 - Clark, David W A1 - Nutile, Teresa A1 - Barnes, Catriona L K A1 - Paul Rhj Timmers A1 - Shen, Xia A1 - Gandin, Ilaria A1 - McDaid, Aaron F A1 - Hansen, Thomas Folkmann A1 - Gordon, Scott D A1 - Giulianini, Franco A1 - Boutin, Thibaud S A1 - Abdellaoui, Abdel A1 - Zhao, Wei A1 - Medina-Gomez, Carolina A1 - Traci M Bartz A1 - Trompet, Stella A1 - Leslie A Lange A1 - Raffield, Laura A1 - van der Spek, Ashley A1 - Galesloot, Tessel E A1 - Proitsi, Petroula A1 - Yanek, Lisa R A1 - Bielak, Lawrence F A1 - Payton, Antony A1 - Murgia, Federico A1 - Concas, Maria Pina A1 - Biino, Ginevra A1 - Tajuddin, Salman M A1 - Seppälä, Ilkka A1 - Amin, Najaf A1 - Boerwinkle, Eric A1 - Børglum, Anders D A1 - Campbell, Archie A1 - Ellen W Demerath A1 - Demuth, Ilja A1 - Jessica Faul A1 - Ford, Ian A1 - Gialluisi, Alessandro A1 - Gögele, Martin A1 - Graff, Mariaelisa A1 - Aroon Hingorani A1 - Jouke-Jan Hottenga A1 - Hougaard, David M A1 - Hurme, Mikko A A1 - Ikram, M Arfan A1 - Jylhä, Marja A1 - Kuh, Diana A1 - Ligthart, Lannie A1 - Lill, Christina M A1 - Lindenberger, Ulman A1 - Lumley, Thomas A1 - Mägi, Reedik A1 - Marques-Vidal, Pedro A1 - Sarah E Medland A1 - Lili Milani A1 - Nagy, Reka A1 - William E R Ollier A1 - Peyser, Patricia A A1 - Pramstaller, Peter P A1 - Ridker, Paul M A1 - Fernando Rivadeneira A1 - Ruggiero, Daniela A1 - Saba, Yasaman A1 - Schmidt, Reinhold A1 - Schmidt, Helena A1 - Slagboom, P Eline A1 - Smith, Blair H A1 - Smith, Jennifer A A1 - Sotoodehnia, Nona A1 - Steinhagen-Thiessen, Elisabeth A1 - van Rooij, Frank J A A1 - Verbeek, André L A1 - Vermeulen, Sita H A1 - Vollenweider, Peter A1 - Wang, Yunpeng A1 - Werge, Thomas A1 - Whitfield, John B A1 - Alan B Zonderman A1 - Lehtimäki, Terho A1 - Michele K Evans A1 - Pirastu, Mario A1 - Fuchsberger, Christian A1 - Bertram, Lars A1 - Pendleton, Neil A1 - Sharon L R Kardia A1 - Ciullo, Marina A1 - Becker, Diane M A1 - Wong, Andrew A1 - Psaty, Bruce M A1 - Cornelia M van Duijn A1 - Wilson, James G A1 - Jukema, J Wouter A1 - Lambertus A Kiemeney A1 - André G Uitterlinden A1 - Franceschini, Nora A1 - Kari E North A1 - David R Weir A1 - Andres Metspalu A1 - Dorret I Boomsma A1 - Caroline Hayward A1 - Daniel I Chasman A1 - Nicholas G Martin A1 - Sattar, Naveed A1 - Campbell, Harry A1 - Tõnu Esko A1 - Kutalik, Zoltán A1 - James F Wilson KW - Alleles KW - Body Mass Index KW - Coronary Disease KW - Education KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - HLA-DQ alpha-Chains KW - HLA-DRB1 Chains KW - Humans KW - Insulin Resistance KW - Life Style KW - Lipoprotein(a) KW - Lipoproteins, HDL KW - Longevity KW - Lung Neoplasms KW - Obesity KW - Polymorphism, Single Nucleotide KW - Smoking KW - Socioeconomic factors AB -

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

VL - 8 IS - 1 ER - TY - JOUR T1 - Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. JF - Nat Genet Y1 - 2016 A1 - Okbay, Aysu A1 - Baselmans, Bart M L A1 - De Neve, Jan-Emmanuel A1 - Turley, Patrick A1 - Nivard, Michel G A1 - Mark Alan Fontana A1 - Meddens, S Fleur W A1 - Richard Karlsson Linnér A1 - Cornelius A Rietveld A1 - Derringer, Jaime A1 - Gratten, Jacob A1 - Lee, James J A1 - Liu, Jimmy Z A1 - de Vlaming, Ronald A1 - Ahluwalia, Tarunveer S A1 - Buchwald, Jadwiga A1 - Cavadino, Alana A1 - Frazier-Wood, Alexis C A1 - Furlotte, Nicholas A A1 - Garfield, Victoria A1 - Geisel, Marie Henrike A1 - Gonzalez, Juan R A1 - Haitjema, Saskia A1 - Karlsson, Robert A1 - van der Laan, Sander W A1 - Ladwig, Karl-Heinz A1 - J. Lahti A1 - Sven J van der Lee A1 - Penelope A Lind A1 - Tian Liu A1 - Lindsay K Matteson A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Minica, Camelia C A1 - Ilja M Nolte A1 - Dennis O Mook-Kanamori A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rawal, Rajesh A1 - Realo, Anu A1 - Rueedi, Rico A1 - Schmidt, Börge A1 - Albert Vernon Smith A1 - Stergiakouli, Evie A1 - Toshiko Tanaka A1 - Kent D Taylor A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Willems, Sara M A1 - Wei Zhao A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Patricia A. Boyle A1 - Cherney, Samantha A1 - Cox, Simon R A1 - Gail Davies A1 - Davis, Oliver S P A1 - Ding, Jun A1 - Nese Direk A1 - Eibich, Peter A1 - Emeny, Rebecca T A1 - Fatemifar, Ghazaleh A1 - Jessica Faul A1 - Luigi Ferrucci A1 - Andreas J Forstner A1 - Gieger, Christian A1 - Gupta, Richa A1 - Tamara B Harris A1 - Harris, Juliette M A1 - Holliday, Elizabeth G A1 - Jouke-Jan Hottenga A1 - Philip L de Jager A1 - Marika A Kaakinen A1 - Kajantie, Eero A1 - Karhunen, Ville A1 - Kolcic, Ivana A1 - Kumari, Meena A1 - Lenore J Launer A1 - Lude L Franke A1 - Li-Gao, Ruifang A1 - Koini, Marisa A1 - Loukola, Anu A1 - Marques-Vidal, Pedro A1 - Grant W Montgomery A1 - Mosing, Miriam A A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Katja E Petrovic A1 - Pulkki-Raback, Laura A1 - Quaye, Lydia A1 - Katri Räikkönen A1 - Rudan, Igor A1 - Rodney J Scott A1 - Jennifer A Smith A1 - Angelina R Sutin A1 - Trzaskowski, Maciej A1 - Anna A E Vinkhuyzen A1 - Lei Yu A1 - Zabaneh, Delilah A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Dorret I Boomsma A1 - Snieder, Harold A1 - Chang, Shun-Chiao A1 - Francesco Cucca A1 - Ian J Deary A1 - Cornelia M van Duijn A1 - Johan G Eriksson A1 - Bültmann, Ute A1 - Eco J. C. de Geus A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - Hansen, Torben A1 - Catharina A Hartman A1 - Haworth, Claire M A A1 - Caroline Hayward A1 - Andrew C Heath A1 - Hinds, David A A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Keltikangas-Järvinen, Liisa A1 - Kraft, Peter A1 - Laura D Kubzansky A1 - Lehtimäki, Terho A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Melinda C Mills A1 - de Mutsert, Renée A1 - Oldehinkel, Albertine J A1 - Pasterkamp, Gerard A1 - Nancy L Pedersen A1 - Plomin, Robert A1 - Polasek, Ozren A1 - Power, Christine A1 - Rich, Stephen S A1 - Rosendaal, Frits R A1 - Hester M. den Ruijter A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Svento, Rauli A1 - Schmidt, Reinhold A1 - Alizadeh, Behrooz Z A1 - Thorkild I. A. Sørensen A1 - Timothy Spector A1 - Andrew Steptoe A1 - Antonio Terracciano A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - André G Uitterlinden A1 - Vollenweider, Peter A1 - Wagner, Gert G A1 - David R Weir A1 - Yang, Jian A1 - Dalton C Conley A1 - Hofman, Albert A1 - Johannesson, Magnus A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Pickrell, Joseph K A1 - Tõnu Esko A1 - Krueger, Robert F A1 - Jonathan P. Beauchamp A1 - Philipp D Koellinger A1 - Daniel J. Benjamin A1 - Bartels, Meike A1 - Cesarini, David KW - Anxiety Disorders KW - Bayes Theorem KW - depression KW - Genome-Wide Association Study KW - Humans KW - Neuroticism KW - Phenotype KW - Polymorphism, Single Nucleotide AB -

Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (|ρ^| ≈ 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.

VL - 48 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27089181?dopt=Abstract ER - TY - JOUR T1 - Genome-wide analysis identifies 12 loci influencing human reproductive behavior. JF - Nat Genet Y1 - 2016 A1 - Nicola Barban A1 - Jansen, Rick A1 - de Vlaming, Ronald A1 - Vaez, Ahmad A1 - Mandemakers, Jornt J A1 - Felix C Tropf A1 - Shen, Xia A1 - James F Wilson A1 - Daniel I Chasman A1 - Ilja M Nolte A1 - Tragante, Vinicius A1 - van der Laan, Sander W A1 - Perry, John R B A1 - Kong, Augustine A1 - Ahluwalia, Tarunveer S A1 - Albrecht, Eva A1 - Laura M Yerges-Armstrong A1 - Atzmon, Gil A1 - Auro, Kirsi A1 - Kristin L. Ayers A1 - Bakshi, Andrew A1 - Ben-Avraham, Danny A1 - Klaus Berger A1 - Bergman, Aviv A1 - Bertram, Lars A1 - Bielak, Lawrence F A1 - Bjornsdottir, Gyda A1 - Bonder, Marc Jan A1 - Broer, Linda A1 - Bui, Minh A1 - Barbieri, Caterina A1 - Cavadino, Alana A1 - Chavarro, Jorge E A1 - Turman, Constance A1 - Maria Pina Concas A1 - Cordell, Heather J A1 - Gail Davies A1 - Eibich, Peter A1 - Eriksson, Nicholas A1 - Tõnu Esko A1 - Eriksson, Joel A1 - Falahi, Fahimeh A1 - Felix, Janine F A1 - Mark Alan Fontana A1 - Lude L Franke A1 - Gandin, Ilaria A1 - Gaskins, Audrey J A1 - Gieger, Christian A1 - Gunderson, Erica P A1 - Guo, Xiuqing A1 - Caroline Hayward A1 - He, Chunyan A1 - Edith Hofer A1 - Huang, Hongyan A1 - Joshi, Peter K A1 - Kanoni, Stavroula A1 - Karlsson, Robert A1 - Kiechl, Stefan A1 - Kifley, Annette A1 - Kluttig, Alexander A1 - Kraft, Peter A1 - Lagou, Vasiliki A1 - Lecoeur, Cecile A1 - Lahti, Jari A1 - Li-Gao, Ruifang A1 - Penelope A Lind A1 - Tian Liu A1 - Makalic, Enes A1 - Mamasoula, Crysovalanto A1 - Lindsay K Matteson A1 - Mbarek, Hamdi A1 - McArdle, Patrick F A1 - McMahon, George A1 - Meddens, S Fleur W A1 - Mihailov, Evelin A1 - Michael B Miller A1 - Missmer, Stacey A A1 - Monnereau, Claire A1 - van der Most, Peter J A1 - Myhre, Ronny A1 - Michael A Nalls A1 - Nutile, Teresa A1 - Ioanna Panagiota Kalafati A1 - Porcu, Eleonora A1 - Prokopenko, Inga A1 - Rajan, Kumar B A1 - Rich-Edwards, Janet A1 - Cornelius A Rietveld A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Rueedi, Rico A1 - Ryan, Kathleen A A1 - Saba, Yasaman A1 - Schmidt, Daniel A1 - Jennifer A Smith A1 - Stolk, Lisette A1 - Streeten, Elizabeth A1 - Tönjes, Anke A1 - Thorleifsson, Gudmar A1 - Ulivi, Sheila A1 - Wedenoja, Juho A1 - Jürgen Wellmann A1 - Willeit, Peter A1 - Yao, Jie A1 - Yengo, Loic A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Zhernakova, Daria V A1 - Amin, Najaf A1 - Andrews, Howard A1 - Balkau, Beverley A1 - Barzilai, Nir A1 - Bergmann, Sven A1 - Biino, Ginevra A1 - Bisgaard, Hans A1 - Bønnelykke, Klaus A1 - Dorret I Boomsma A1 - Buring, Julie E A1 - Campbell, Harry A1 - Cappellani, Stefania A1 - Ciullo, Marina A1 - Cox, Simon R A1 - Francesco Cucca A1 - Toniolo, Daniela A1 - Davey-Smith, George A1 - Ian J Deary A1 - George Dedoussis A1 - Deloukas, Panos A1 - Cornelia M van Duijn A1 - Eco J. C. de Geus A1 - Johan G Eriksson A1 - Jessica Faul A1 - Cinzia Felicita Sala A1 - Froguel, Philippe A1 - Paolo P. Gasparini A1 - Giorgia G Girotto A1 - Hans-Jörgen Grabe A1 - Greiser, Karin Halina A1 - Groenen, Patrick J F A1 - de Haan, Hugoline G A1 - Haerting, Johannes A1 - Tamara B Harris A1 - Andrew C Heath A1 - Heikkilä, Kauko A1 - Hofman, Albert A1 - Homuth, Georg A1 - Holliday, Elizabeth G A1 - John L Hopper A1 - Hyppönen, Elina A1 - Jacobsson, Bo A1 - Vincent Jaddoe A1 - Johannesson, Magnus A1 - Jugessur, Astanand A1 - Kähönen, Mika A1 - Kajantie, Eero A1 - Sharon L R Kardia A1 - Keavney, Bernard A1 - Kolcic, Ivana A1 - Koponen, Päivikki A1 - Kovacs, Peter A1 - Kronenberg, Florian A1 - Kutalik, Zoltán A1 - La Bianca, Martina A1 - Lachance, Genevieve A1 - Iacono, William G A1 - Lai, Sandra A1 - Lehtimäki, Terho A1 - David C Liewald A1 - Lindgren, Cecilia M A1 - Yongmei Liu A1 - Luben, Robert A1 - Lucht, Michael A1 - Luoto, Riitta A1 - Magnus, Per A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - McQuillan, Ruth A1 - Sarah E Medland A1 - Meisinger, Christa A1 - Mellström, Dan A1 - Andres Metspalu A1 - Traglia, Michela A1 - Lili Milani A1 - Mitchell, Paul A1 - Grant W Montgomery A1 - Dennis O Mook-Kanamori A1 - de Mutsert, Renée A1 - Nohr, Ellen A A1 - Ohlsson, Claes A1 - Olsen, Jørn A1 - Ong, Ken K A1 - Paternoster, Lavinia A1 - Pattie, Alison A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Peyser, Patricia A A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Power, Chris A1 - Kaprio, Jaakko A1 - Raffel, Leslie J A1 - Katri Räikkönen A1 - Olli T Raitakari A1 - Ridker, Paul M A1 - Ring, Susan M A1 - Roll, Kathryn A1 - Rudan, Igor A1 - Ruggiero, Daniela A1 - Rujescu, Dan A1 - Veikko Salomaa A1 - Schlessinger, David A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Schupf, Nicole A1 - Johannes H Smit A1 - Sorice, Rossella A1 - Timothy Spector A1 - John M Starr A1 - Stöckl, Doris A1 - Strauch, Konstantin A1 - Stumvoll, Michael A1 - Swertz, Morris A A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vaccargiu, Simona A1 - Viikari, Jorma A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Vollenweider, Peter A1 - Vuckovic, Dragana A1 - Waage, Johannes A1 - Wagner, Gert G A1 - Wang, Jie Jin A1 - Wareham, Nicholas J A1 - David R Weir A1 - Gonneke Willemsen A1 - Willeit, Johann A1 - Alan F Wright A1 - Krina T Zondervan A1 - Stefansson, Kari A1 - Krueger, Robert F A1 - Lee, James J A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger A1 - den Hoed, Marcel A1 - Snieder, Harold A1 - Melinda C Mills AB -

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

VL - 48 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27798627?dopt=Abstract ER - TY - JOUR T1 - Genome-wide association study identifies 74 loci associated with educational attainment. JF - Nature Y1 - 2016 A1 - Okbay, Aysu A1 - Jonathan P. Beauchamp A1 - Mark Alan Fontana A1 - Lee, James J A1 - Pers, Tune H A1 - Cornelius A Rietveld A1 - Turley, Patrick A1 - Chen, Guo-Bo A1 - Emilsson, Valur A1 - Meddens, S Fleur W A1 - Oskarsson, Sven A1 - Pickrell, Joseph K A1 - Thom, Kevin A1 - Pascal N Timshel A1 - de Vlaming, Ronald A1 - Abdel Abdellaoui A1 - Ahluwalia, Tarunveer S A1 - Bacelis, Jonas A1 - Baumbach, Clemens A1 - Bjornsdottir, Gyda A1 - Brandsma, Johannes H A1 - Maria Pina Concas A1 - Derringer, Jaime A1 - Furlotte, Nicholas A A1 - Galesloot, Tessel E A1 - Giorgia G Girotto A1 - Gupta, Richa A1 - Hall, Leanne M A1 - Sarah E Harris A1 - Edith Hofer A1 - Horikoshi, Momoko A1 - Huffman, Jennifer E A1 - Kaasik, Kadri A1 - Ioanna Panagiota Kalafati A1 - Karlsson, Robert A1 - Kong, Augustine A1 - Lahti, Jari A1 - Sven J van der Lee A1 - Christiaan de Leeuw A1 - Penelope A Lind A1 - Lindgren, Karl-Oskar A1 - Tian Liu A1 - Mangino, Massimo A1 - Marten, Jonathan A1 - Mihailov, Evelin A1 - Michael B Miller A1 - van der Most, Peter J A1 - Christopher J Oldmeadow A1 - Payton, Antony A1 - Pervjakova, Natalia A1 - Wouter J Peyrot A1 - Qian, Yong A1 - Olli T Raitakari A1 - Rueedi, Rico A1 - Salvi, Erika A1 - Schmidt, Börge A1 - Schraut, Katharina E A1 - Jianxin Shi A1 - Albert Vernon Smith A1 - Poot, Raymond A A1 - St Pourcain, Beate A1 - Teumer, Alexander A1 - Thorleifsson, Gudmar A1 - Verweij, Niek A1 - Vuckovic, Dragana A1 - Jürgen Wellmann A1 - Westra, Harm-Jan A1 - Yang, Jingyun A1 - Wei Zhao A1 - Zhihong Zhu A1 - Alizadeh, Behrooz Z A1 - Amin, Najaf A1 - Bakshi, Andrew A1 - Baumeister, Sebastian E A1 - Biino, Ginevra A1 - Bønnelykke, Klaus A1 - Patricia A. Boyle A1 - Campbell, Harry A1 - Cappuccio, Francesco P A1 - Gail Davies A1 - De Neve, Jan-Emmanuel A1 - Deloukas, Panos A1 - Demuth, Ilja A1 - Ding, Jun A1 - Eibich, Peter A1 - Eisele, Lewin A1 - Eklund, Niina A1 - Jessica Faul A1 - Feitosa, Mary F A1 - Andreas J Forstner A1 - Gandin, Ilaria A1 - Gunnarsson, Bjarni A1 - Halldórsson, Bjarni V A1 - Tamara B Harris A1 - Andrew C Heath A1 - Lynne J Hocking A1 - Holliday, Elizabeth G A1 - Homuth, Georg A1 - Horan, Michael A A1 - Jouke-Jan Hottenga A1 - Philip L de Jager A1 - Joshi, Peter K A1 - Jugessur, Astanand A1 - Marika A Kaakinen A1 - Kähönen, Mika A1 - Kanoni, Stavroula A1 - Keltigangas-Järvinen, Liisa A1 - Lambertus A Kiemeney A1 - Kolcic, Ivana A1 - Koskinen, Seppo A1 - Kraja, Aldi T A1 - Kroh, Martin A1 - Kutalik, Zoltán A1 - Latvala, Antti A1 - Lenore J Launer A1 - Lebreton, Maël P A1 - Douglas F Levinson A1 - Paul Lichtenstein A1 - Lichtner, Peter A1 - David C Liewald A1 - Loukola, Anu A1 - Pamela A F Madden A1 - Mägi, Reedik A1 - Mäki-Opas, Tomi A1 - Riccardo E Marioni A1 - Marques-Vidal, Pedro A1 - Meddens, Gerardus A A1 - McMahon, George A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Milaneschi, Yusplitri A1 - Lili Milani A1 - Grant W Montgomery A1 - Myhre, Ronny A1 - Nelson, Christopher P A1 - Nyholt, Dale R A1 - William E R Ollier A1 - Aarno Palotie A1 - Paternoster, Lavinia A1 - Nancy L Pedersen A1 - Katja E Petrovic A1 - David J Porteous A1 - Katri Räikkönen A1 - Ring, Susan M A1 - Robino, Antonietta A1 - Rostapshova, Olga A1 - Rudan, Igor A1 - Rustichini, Aldo A1 - Veikko Salomaa A1 - Sanders, Alan R A1 - Sarin, Antti-Pekka A1 - Schmidt, Helena A1 - Rodney J Scott A1 - Smith, Blair H A1 - Jennifer A Smith A1 - Staessen, Jan A A1 - Steinhagen-Thiessen, Elisabeth A1 - Strauch, Konstantin A1 - Antonio Terracciano A1 - Tobin, Martin D A1 - Ulivi, Sheila A1 - Vaccargiu, Simona A1 - Quaye, Lydia A1 - van Rooij, Frank J A A1 - Venturini, Cristina A1 - Anna A E Vinkhuyzen A1 - Völker, Uwe A1 - Völzke, Henry A1 - Vonk, Judith M A1 - Vozzi, Diego A1 - Waage, Johannes A1 - Erin B Ware A1 - Gonneke Willemsen A1 - John R. Attia A1 - David A Bennett A1 - Klaus Berger A1 - Bertram, Lars A1 - Bisgaard, Hans A1 - Dorret I Boomsma A1 - Ingrid B Borecki A1 - Bültmann, Ute A1 - Chabris, Christopher F A1 - Francesco Cucca A1 - Cusi, Daniele A1 - Ian J Deary A1 - George Dedoussis A1 - Cornelia M van Duijn A1 - Johan G Eriksson A1 - Franke, Barbara A1 - Lude L Franke A1 - Paolo P. Gasparini A1 - Gejman, Pablo V A1 - Gieger, Christian A1 - Hans-Jörgen Grabe A1 - Gratten, Jacob A1 - Groenen, Patrick J F A1 - Gudnason, Vilmundur A1 - van der Harst, Pim A1 - Caroline Hayward A1 - Hinds, David A A1 - Hoffmann, Wolfgang A1 - Hyppönen, Elina A1 - Iacono, William G A1 - Jacobsson, Bo A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Kaprio, Jaakko A1 - Sharon L R Kardia A1 - Lehtimäki, Terho A1 - Lehrer, Steven F A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - Andres Metspalu A1 - Pendleton, Neil A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Nicola Pirastu A1 - Pirastu, Mario A1 - Polasek, Ozren A1 - Posthuma, Danielle A1 - Power, Christine A1 - Province, Michael A A1 - Nilesh J Samani A1 - Schlessinger, David A1 - Schmidt, Reinhold A1 - Thorkild I. A. Sørensen A1 - Timothy Spector A1 - Stefansson, Kari A1 - Thorsteinsdottir, Unnur A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - Henning Tiemeier A1 - Tung, Joyce Y A1 - André G Uitterlinden A1 - Vitart, Veronique A1 - Vollenweider, Peter A1 - David R Weir A1 - James F Wilson A1 - Alan F Wright A1 - Dalton C Conley A1 - Krueger, Robert F A1 - George Davey Smith A1 - Hofman, Albert A1 - David I Laibson A1 - Sarah E Medland A1 - Meyer, Michelle N A1 - Yang, Jian A1 - Johannesson, Magnus A1 - Peter M Visscher A1 - Tõnu Esko A1 - Philipp D Koellinger A1 - Cesarini, David A1 - Daniel J. Benjamin KW - Alzheimer's disease KW - Bipolar Disorder KW - Cognitive Ability KW - Education KW - Fetus KW - Genome-Wide Association Study KW - Humans KW - Molecular Sequence Annotation KW - Polymorphism, Single Nucleotide KW - Schizophrenia KW - United Kingdom AB -

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

VL - 533 IS - 7604 U1 - http://www.ncbi.nlm.nih.gov/pubmed/27225129?dopt=Abstract ER - TY - JOUR T1 - The association between lower educational attainment and depression owing to shared genetic effects? Results in ~25,000 subjects. JF - Mol Psychiatry Y1 - 2015 A1 - Wouter J Peyrot A1 - Lee, S H A1 - Milaneschi, Y A1 - Abdel Abdellaoui A1 - Byrne, E M A1 - Tõnu Esko A1 - Eco J. C. de Geus A1 - Hemani, G A1 - Jouke-Jan Hottenga A1 - Kloiber, S A1 - Douglas F Levinson A1 - Lucae, S A1 - Nicholas G Martin A1 - Sarah E Medland A1 - Andres Metspalu A1 - Lili Milani A1 - Markus M Nöthen A1 - Potash, J B A1 - Rietschel, M A1 - Cornelius A Rietveld A1 - Ripke, S A1 - Jianxin Shi A1 - Gonneke Willemsen A1 - Zhihong Zhu A1 - Dorret I Boomsma A1 - Naomi R. Wray A1 - Brenda W J H Penninx KW - Adult KW - Aged KW - Cohort Studies KW - Depressive Disorder, Major KW - Educational Status KW - Estonia KW - Female KW - Gene-Environment Interaction KW - Genetic Association Studies KW - Genotype KW - Humans KW - Likelihood Functions KW - Male KW - Middle Aged KW - Netherlands KW - Odds Ratio KW - Polymorphism, Single Nucleotide KW - Psychiatric Status Rating Scales KW - Regression Analysis AB -

An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14,949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15,138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884,105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on ~120,000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status.

VL - 20 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25917368?dopt=Abstract ER - TY - JOUR T1 - Directional dominance on stature and cognition in diverse human populations. JF - Nature Y1 - 2015 A1 - Joshi, Peter K A1 - Tõnu Esko A1 - Mattsson, Hannele A1 - Eklund, Niina A1 - Gandin, Ilaria A1 - Nutile, Teresa A1 - Jackson, Anne U A1 - Schurmann, Claudia A1 - Albert Vernon Smith A1 - Zhang, Weihua A1 - Okada, Yukinori A1 - Stančáková, Alena A1 - Jessica Faul A1 - Wei Zhao A1 - Traci M Bartz A1 - Maria Pina Concas A1 - Franceschini, Nora A1 - Enroth, Stefan A1 - Vitart, Veronique A1 - Trompet, Stella A1 - Guo, Xiuqing A1 - Daniel I Chasman A1 - Jeff O'Connell A1 - Corre, Tanguy A1 - Nongmaithem, Suraj S A1 - Chen, Yuning A1 - Mangino, Massimo A1 - Ruggiero, Daniela A1 - Traglia, Michela A1 - Farmaki, Aliki-Eleni A1 - Kacprowski, Tim A1 - Bjonnes, Andrew A1 - van der Spek, Ashley A1 - Wu, Ying A1 - Giri, Anil K A1 - Yanek, Lisa R A1 - Wang, Lihua A1 - Edith Hofer A1 - Cornelius A Rietveld A1 - McLeod, Olga A1 - Marilyn C Cornelis A1 - Pattaro, Cristian A1 - Verweij, Niek A1 - Baumbach, Clemens A1 - Abdel Abdellaoui A1 - Warren, Helen R A1 - Vuckovic, Dragana A1 - Mei, Hao A1 - Bouchard, Claude A1 - Perry, John R B A1 - Cappellani, Stefania A1 - Saira S Mirza A1 - Benton, Miles C A1 - Broeckel, Ulrich A1 - Sarah E Medland A1 - Penelope A Lind A1 - Malerba, Giovanni A1 - Alexander W Drong A1 - Yengo, Loic A1 - Bielak, Lawrence F A1 - Zhi, Degui A1 - van der Most, Peter J A1 - Daniel Shriner A1 - Mägi, Reedik A1 - Hemani, Gibran A1 - Karaderi, Tugce A1 - Wang, Zhaoming A1 - Tian Liu A1 - Demuth, Ilja A1 - Jing Hua Zhao A1 - Meng, Weihua A1 - Lataniotis, Lazaros A1 - van der Laan, Sander W A1 - Bradfield, Jonathan P A1 - Andrew R Wood A1 - Bonnefond, Amelie A1 - Ahluwalia, Tarunveer S A1 - Hall, Leanne M A1 - Salvi, Erika A1 - Yazar, Seyhan A1 - Carstensen, Lisbeth A1 - de Haan, Hugoline G A1 - Abney, Mark A1 - Afzal, Uzma A1 - Matthew A. Allison A1 - Amin, Najaf A1 - Asselbergs, Folkert W A1 - Bakker, Stephan J L A1 - Barr, R Graham A1 - Baumeister, Sebastian E A1 - Daniel J. Benjamin A1 - Bergmann, Sven A1 - Boerwinkle, Eric A1 - Erwin P Bottinger A1 - Campbell, Archie A1 - Chakravarti, Aravinda A1 - Chan, Yingleong A1 - Chanock, Stephen J A1 - Chen, Constance A1 - Yii-Der I Chen A1 - Collins, Francis S A1 - Connell, John A1 - Correa, Adolfo A1 - Cupples, L Adrienne A1 - Gail Davies A1 - Dörr, Marcus A1 - Georg B Ehret A1 - Ellis, Stephen B A1 - Feenstra, Bjarke A1 - Feitosa, Mary F A1 - Ford, Ian A1 - Caroline S Fox A1 - Timothy M Frayling A1 - Friedrich, Nele A1 - Geller, Frank A1 - Scotland, Generation A1 - Gillham-Nasenya, Irina A1 - Gottesman, Omri A1 - Graff, Misa A1 - Grodstein, Francine A1 - Gu, Charles A1 - Haley, Chris A1 - Hammond, Christopher J A1 - Sarah E Harris A1 - Tamara B Harris A1 - Nicholas D Hastie A1 - Heard-Costa, Nancy L A1 - Heikkilä, Kauko A1 - Lynne J Hocking A1 - Homuth, Georg A1 - Jouke-Jan Hottenga A1 - Huang, Jinyan A1 - Huffman, Jennifer E A1 - Hysi, Pirro G A1 - Mohammed Arfan Ikram A1 - Ingelsson, Erik A1 - Joensuu, Anni A1 - Johansson, Åsa A1 - Jousilahti, Pekka A1 - Jukema, J Wouter A1 - Kähönen, Mika A1 - Kamatani, Yoichiro A1 - Kanoni, Stavroula A1 - Kerr, Shona M A1 - Khan, Nazir M A1 - Philipp D Koellinger A1 - Koistinen, Heikki A A1 - Kooner, Manraj K A1 - Kubo, Michiaki A1 - Kuusisto, Johanna A1 - Lahti, Jari A1 - Lenore J Launer A1 - Lea, Rodney A A1 - Lehne, Benjamin A1 - Lehtimäki, Terho A1 - David C Liewald A1 - Lars Lind A1 - Loh, Marie A1 - Lokki, Marja-Liisa A1 - London, Stephanie J A1 - Loomis, Stephanie J A1 - Loukola, Anu A1 - Lu, Yingchang A1 - Lumley, Thomas A1 - Lundqvist, Annamari A1 - Männistö, Satu A1 - Marques-Vidal, Pedro A1 - Masciullo, Corrado A1 - Matchan, Angela A1 - Mathias, Rasika A A1 - Matsuda, Koichi A1 - Meigs, James B A1 - Meisinger, Christa A1 - Meitinger, Thomas A1 - Menni, Cristina A1 - Mentch, Frank D A1 - Mihailov, Evelin A1 - Lili Milani A1 - Montasser, May E A1 - Grant W Montgomery A1 - Alanna C Morrison A1 - Myers, Richard H A1 - Nadukuru, Rajiv A1 - Navarro, Pau A1 - Nelis, Mari A1 - Nieminen, Markku S A1 - Ilja M Nolte A1 - O'Connor, George T A1 - Ogunniyi, Adesola A1 - Padmanabhan, Sandosh A1 - Walter R Palmas A1 - Pankow, James S A1 - Patarcic, Inga A1 - Pavani, Francesca A1 - Peyser, Patricia A A1 - Pietilainen, Kirsi A1 - Neil Poulter A1 - Prokopenko, Inga A1 - Ralhan, Sarju A1 - Redmond, Paul A1 - Rich, Stephen S A1 - Rissanen, Harri A1 - Robino, Antonietta A1 - Rose, Lynda M A1 - Rose, Richard A1 - Cinzia Felicita Sala A1 - Babatunde Salako A1 - Veikko Salomaa A1 - Sarin, Antti-Pekka A1 - Saxena, Richa A1 - Schmidt, Helena A1 - Scott, Laura J A1 - Scott, William R A1 - Sennblad, Bengt A1 - Seshadri, Sudha A1 - Peter Sever A1 - Shrestha, Smeeta A1 - Smith, Blair H A1 - Jennifer A Smith A1 - Soranzo, Nicole A1 - Sotoodehnia, Nona A1 - Southam, Lorraine A1 - Stanton, Alice V A1 - Stathopoulou, Maria G A1 - Strauch, Konstantin A1 - Strawbridge, Rona J A1 - Suderman, Matthew J A1 - Tandon, Nikhil A1 - Tang, Sian-Tsun A1 - Kent D Taylor A1 - Bamidele O Tayo A1 - Töglhofer, Anna Maria A1 - Tomaszewski, Maciej A1 - Tšernikova, Natalia A1 - Tuomilehto, Jaakko A1 - André G Uitterlinden A1 - Vaidya, Dhananjay A1 - van Hylckama Vlieg, Astrid A1 - van Setten, Jessica A1 - Vasankari, Tuula A1 - Vedantam, Sailaja A1 - Vlachopoulou, Efthymia A1 - Vozzi, Diego A1 - Vuoksimaa, Eero A1 - Waldenberger, Melanie A1 - Erin B Ware A1 - Wentworth-Shields, William A1 - Whitfield, John B A1 - Sarah Wild A1 - Gonneke Willemsen A1 - Yajnik, Chittaranjan S A1 - Yao, Jie A1 - Zaza, Gianluigi A1 - Zhu, Xiaofeng A1 - Salem, Rany M A1 - Melbye, Mads A1 - Bisgaard, Hans A1 - Nilesh J Samani A1 - Cusi, Daniele A1 - Mackey, David A A1 - Cooper, Richard S A1 - Froguel, Philippe A1 - Pasterkamp, Gerard A1 - Grant, Struan F A A1 - Hakonarson, Hakon A1 - Luigi Ferrucci A1 - Scott, Robert A A1 - Morris, Andrew D A1 - Palmer, Colin N A A1 - George Dedoussis A1 - Deloukas, Panos A1 - Bertram, Lars A1 - Lindenberger, Ulman A1 - Berndt, Sonja I A1 - Lindgren, Cecilia M A1 - Nicholas J Timpson A1 - Tönjes, Anke A1 - Munroe, Patricia B A1 - Thorkild I. A. Sørensen A1 - Charles N Rotimi A1 - Donna K Arnett A1 - Oldehinkel, Albertine J A1 - Sharon L R Kardia A1 - Balkau, Beverley A1 - Gambaro, Giovanni A1 - Morris, Andrew P A1 - Johan G Eriksson A1 - Margaret J Wright A1 - Nicholas G Martin A1 - Hunt, Steven C A1 - John M Starr A1 - Ian J Deary A1 - Griffiths, Lyn R A1 - Henning Tiemeier A1 - Nicola Pirastu A1 - Kaprio, Jaakko A1 - Wareham, Nicholas J A1 - Pérusse, Louis A1 - Wilson, James G A1 - Giorgia G Girotto A1 - Caulfield, Mark J A1 - Olli T Raitakari A1 - Dorret I Boomsma A1 - Gieger, Christian A1 - van der Harst, Pim A1 - Hicks, Andrew A A1 - Kraft, Peter A1 - Sinisalo, Juha A1 - Knekt, Paul A1 - Johannesson, Magnus A1 - Patrik K E Magnusson A1 - Hamsten, Anders A1 - Schmidt, Reinhold A1 - Ingrid B Borecki A1 - Vartiainen, Erkki A1 - Becker, Diane M A1 - Bharadwaj, Dwaipayan A1 - Mohlke, Karen L A1 - Boehnke, Michael A1 - Cornelia M van Duijn A1 - Sanghera, Dharambir K A1 - Teumer, Alexander A1 - Zeggini, Eleftheria A1 - Andres Metspalu A1 - Paolo P. Gasparini A1 - Ulivi, Sheila A1 - Ober, Carole A1 - Toniolo, Daniela A1 - Rudan, Igor A1 - David J Porteous A1 - Ciullo, Marina A1 - Timothy Spector A1 - Caroline Hayward A1 - Dupuis, Josée A1 - Ruth J F Loos A1 - Alan F Wright A1 - Chandak, Giriraj R A1 - Vollenweider, Peter A1 - Alan R Shuldiner A1 - Ridker, Paul M A1 - Rotter, Jerome I A1 - Sattar, Naveed A1 - Gyllensten, Ulf A1 - Kari E North A1 - Pirastu, Mario A1 - Psaty, Bruce M A1 - David R Weir A1 - Laakso, Markku A1 - Gudnason, Vilmundur A1 - Takahashi, Atsushi A1 - Chambers, John C A1 - Kooner, Jaspal S A1 - David P Strachan A1 - Campbell, Harry A1 - Joel N Hirschhron A1 - Markus Perola A1 - Polasek, Ozren A1 - James F Wilson KW - Biological Evolution KW - Blood pressure KW - Body Height KW - Cholesterol KW - Cognitive Ability KW - Cohort Studies KW - Education KW - Female KW - Forced Expiratory Volume KW - Genome KW - Homozygote KW - Humans KW - Lung Volume Measurements KW - Male KW - Phenotype AB -

Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.

VL - 523 IS - 7561 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26131930?dopt=Abstract ER - TY - JOUR T1 - Genetic studies of body mass index yield new insights for obesity biology. JF - Nature Y1 - 2015 A1 - Locke, Adam E A1 - Kahali, Bratati A1 - Berndt, Sonja I A1 - Justice, Anne E A1 - Pers, Tune H A1 - Day, Felix R A1 - Powell, Corey A1 - Vedantam, Sailaja A1 - Buchkovich, Martin L A1 - Yang, Jian A1 - Croteau-Chonka, Damien C A1 - Tõnu Esko A1 - Fall, Tove A1 - Ferreira, Teresa A1 - Gustafsson, Stefan A1 - Kutalik, Zoltán A1 - Luan, Jian'an A1 - Mägi, Reedik A1 - Randall, Joshua C A1 - Thomas W Winkler A1 - Andrew R Wood A1 - Workalemahu, Tsegaselassie A1 - Jessica Faul A1 - Jennifer A Smith A1 - Jing Hua Zhao A1 - Wei Zhao A1 - Chen, Jin A1 - Rudolf Ferhmann A1 - Hedman, Åsa K A1 - Karjalainen, Juha A1 - Schmidt, Ellen M A1 - Absher, Devin A1 - Amin, Najaf A1 - Anderson, Denise A1 - Beekman, Marian A1 - Bolton, Jennifer L A1 - Bragg-Gresham, Jennifer L A1 - Buyske, Steven A1 - Demirkan, Ayse A1 - Deng, Guohong A1 - Georg B Ehret A1 - Feenstra, Bjarke A1 - Feitosa, Mary F A1 - Fischer, Krista A1 - Goel, Anuj A1 - Gong, Jian A1 - Jackson, Anne U A1 - Kanoni, Stavroula A1 - Kleber, Marcus E A1 - Kristiansson, Kati A1 - Lim, Unhee A1 - Lotay, Vaneet A1 - Mangino, Massimo A1 - Irene Mateo Leach A1 - Medina-Gomez, Carolina A1 - Sarah E Medland A1 - Michael A Nalls A1 - Palmer, Cameron D A1 - Pasko, Dorota A1 - Pechlivanis, Sonali A1 - Peters, Marjolein J A1 - Prokopenko, Inga A1 - Shungin, Dmitry A1 - Stančáková, Alena A1 - Strawbridge, Rona J A1 - Yun Ju Sung A1 - Toshiko Tanaka A1 - Teumer, Alexander A1 - Trompet, Stella A1 - van der Laan, Sander W A1 - van Setten, Jessica A1 - Jana V. van Vliet-Ostaptchouk A1 - Wang, Zhaoming A1 - Yengo, Loic A1 - Zhang, Weihua A1 - Isaacs, Aaron A1 - Albrecht, Eva A1 - Ärnlöv, Johan A1 - Arscott, Gillian M A1 - Attwood, Antony P A1 - Bandinelli, Stefania A1 - Barrett, Amy A1 - Bas, Isabelita N A1 - Bellis, Claire A1 - Bennett, Amanda J A1 - Berne, Christian A1 - Blagieva, Roza A1 - Blüher, Matthias A1 - Böhringer, Stefan A1 - Bonnycastle, Lori L A1 - Böttcher, Yvonne A1 - Boyd, Heather A A1 - Bruinenberg, Marcel A1 - Caspersen, Ida H A1 - Yii-Der I Chen A1 - Robert Clark A1 - Daw, E Warwick A1 - de Craen, Anton J M A1 - Delgado, Graciela A1 - Dimitriou, Maria A1 - Doney, Alex S F A1 - Eklund, Niina A1 - Estrada, Karol A1 - Eury, Elodie A1 - Folkersen, Lasse A1 - Fraser, Ross M A1 - Melissa E Garcia A1 - Geller, Frank A1 - Giedraitis, Vilmantas A1 - Gigante, Bruna A1 - Alan S Go A1 - Golay, Alain A1 - Goodall, Alison H A1 - Gordon, Scott D A1 - Gorski, Mathias A1 - Hans-Jörgen Grabe A1 - Grallert, Harald A1 - Grammer, Tanja B A1 - Gräßler, Jürgen A1 - Grönberg, Henrik A1 - Groves, Christopher J A1 - Gusto, Gaëlle A1 - Jeffrey Haessler A1 - Hall, Per A1 - Haller, Toomas A1 - Hallmans, Göran A1 - Catharina A Hartman A1 - Hassinen, Maija A1 - Caroline Hayward A1 - Heard-Costa, Nancy L A1 - Helmer, Quinta A1 - Hengstenberg, Christian A1 - Oddgeir L Holmen A1 - Jouke-Jan Hottenga A1 - James, Alan L A1 - Janina Jeff A1 - Johansson, Åsa A1 - Jolley, Jennifer A1 - Juliusdottir, Thorhildur A1 - Kinnunen, Leena A1 - Koenig, Wolfgang A1 - Koskenvuo, Markku A1 - Kratzer, Wolfgang A1 - Laitinen, Jaana A1 - Lamina, Claudia A1 - Leander, Karin A1 - Lee, Nanette R A1 - Lichtner, Peter A1 - Lars Lind A1 - Lindström, Jaana A1 - Ken Sin Lo A1 - Lobbens, Stéphane A1 - Lorbeer, Roberto A1 - Lu, Yingchang A1 - Mach, François A1 - Patrik K E Magnusson A1 - Mahajan, Anubha A1 - McArdle, Wendy L A1 - McLachlan, Stela A1 - Menni, Cristina A1 - Merger, Sigrun A1 - Mihailov, Evelin A1 - Lili Milani A1 - Moayyeri, Alireza A1 - Monda, Keri L A1 - Morken, Mario A A1 - Mulas, Antonella A1 - Müller, Gabriele A1 - Müller-Nurasyid, Martina A1 - Musk, Arthur W A1 - Nagaraja, Ramaiah A1 - Markus M Nöthen A1 - Ilja M Nolte A1 - Pilz, Stefan A1 - Nigel W Rayner A1 - Renstrom, Frida A1 - Rettig, Rainer A1 - Ried, Janina S A1 - Ripke, Stephan A1 - Neil R Robertson A1 - Rose, Lynda M A1 - Sanna, Serena A1 - Scharnagl, Hubert A1 - Scholtens, Salome A1 - Schumacher, Fredrick R A1 - Scott, William R A1 - Seufferlein, Thomas A1 - Jianxin Shi A1 - Albert Vernon Smith A1 - Smolonska, Joanna A1 - Stanton, Alice V A1 - Steinthorsdottir, Valgerdur A1 - Kathleen E Stirrups A1 - Heather M Stringham A1 - Sundström, Johan A1 - Swertz, Morris A A1 - Swift, Amy J A1 - Syvänen, Ann-Christine A1 - Tan, Sian-Tsung A1 - Bamidele O Tayo A1 - Thorand, Barbara A1 - Thorleifsson, Gudmar A1 - Tyrer, Jonathan P A1 - Uh, Hae-Won A1 - Vandenput, Liesbeth A1 - Verhulst, Frank C A1 - Vermeulen, Sita H A1 - Verweij, Niek A1 - Vonk, Judith M A1 - Lindsay L Waite A1 - Warren, Helen R A1 - Dawn M Waterworth A1 - Michael N Weedon A1 - Wilkens, Lynne R A1 - Willenborg, Christina A1 - Wilsgaard, Tom A1 - Wojczynski, Mary K A1 - Wong, Andrew A1 - Alan F Wright A1 - Zhang, Qunyuan A1 - Brennan, Eoin P A1 - Murim Choi A1 - Dastani, Zari A1 - Alexander W Drong A1 - Eriksson, Per A1 - Franco-Cereceda, Anders A1 - Gådin, Jesper R A1 - Gharavi, Ali G A1 - Goddard, Michael E A1 - Handsaker, Robert E A1 - Huang, Jinyan A1 - Karpe, Fredrik A1 - Kathiresan, Sekar A1 - Keildson, Sarah A1 - Kiryluk, Krzysztof A1 - Kubo, Michiaki A1 - Lee, Jong-Young A1 - Liang, Liming A1 - Lifton, Richard P A1 - Ma, Baoshan A1 - McCarroll, Steven A A1 - McKnight, Amy J A1 - Min, Josine L A1 - Moffatt, Miriam F A1 - Grant W Montgomery A1 - Joanne M Murabito A1 - Nicholson, George A1 - Nyholt, Dale R A1 - Okada, Yukinori A1 - Perry, John R B A1 - Dorajoo, Rajkumar A1 - Reinmaa, Eva A1 - Salem, Rany M A1 - Sandholm, Niina A1 - Scott, Robert A A1 - Stolk, Lisette A1 - Takahashi, Atsushi A1 - Tanaka, Toshihiro A1 - Ferdinand M van 't Hooft A1 - Anna A E Vinkhuyzen A1 - Westra, Harm-Jan A1 - Wei Zhang A1 - Krina T Zondervan A1 - Andrew C Heath A1 - Arveiler, Dominique A1 - Bakker, Stephan J L A1 - Beilby, John A1 - Bergman, Richard N A1 - Blangero, John A1 - Bovet, Pascal A1 - Campbell, Harry A1 - Caulfield, Mark J A1 - Cesana, Giancarlo A1 - Chakravarti, Aravinda A1 - Daniel I Chasman A1 - Chines, Peter S A1 - Collins, Francis S A1 - Crawford, Dana C A1 - Cupples, L Adrienne A1 - Cusi, Daniele A1 - Danesh, John A1 - de Faire, Ulf A1 - Hester M den Ruijter A1 - Dominiczak, Anna F A1 - Erbel, Raimund A1 - Erdmann, Jeanette A1 - Johan G Eriksson A1 - Farrall, Martin A1 - Felix, Stephan B A1 - Ferrannini, Ele A1 - Ferrières, Jean A1 - Ford, Ian A1 - Forouhi, Nita G A1 - Forrester, Terrence A1 - Franco, Oscar H A1 - Gansevoort, Ron T A1 - Gejman, Pablo V A1 - Gieger, Christian A1 - Gottesman, Omri A1 - Gudnason, Vilmundur A1 - Gyllensten, Ulf A1 - Hall, Alistair S A1 - Tamara B Harris A1 - Andrew T Hattersley A1 - Hicks, Andrew A A1 - Hindorff, Lucia A A1 - Aroon Hingorani A1 - Hofman, Albert A1 - Homuth, Georg A1 - Hovingh, G Kees A1 - Humphries, Steve E A1 - Hunt, Steven C A1 - Hyppönen, Elina A1 - Illig, Thomas A1 - Jacobs, Kevin B A1 - Järvelin, Marjo-Riitta A1 - Jöckel, Karl-Heinz A1 - Johansen, Berit A1 - Jousilahti, Pekka A1 - Jukema, J Wouter A1 - Jula, Antti M A1 - Kaprio, Jaakko A1 - Kastelein, John J P A1 - Keinanen-Kiukaanniemi, Sirkka M A1 - Lambertus A Kiemeney A1 - Knekt, Paul A1 - Kooner, Jaspal S A1 - Charles Kooperberg A1 - Kovacs, Peter A1 - Kraja, Aldi T A1 - Kumari, Meena A1 - Kuusisto, Johanna A1 - Lakka, Timo A A1 - Langenberg, Claudia A1 - Loic Le Marchand A1 - Lehtimäki, Terho A1 - Lyssenko, Valeriya A1 - Männistö, Satu A1 - Marette, André A1 - Matise, Tara C A1 - McKenzie, Colin A A1 - McKnight, Barbara A1 - Moll, Frans L A1 - Morris, Andrew D A1 - Morris, Andrew P A1 - Murray, Jeffrey C A1 - Nelis, Mari A1 - Ohlsson, Claes A1 - Oldehinkel, Albertine J A1 - Ong, Ken K A1 - Pamela A F Madden A1 - Pasterkamp, Gerard A1 - Peden, John F A1 - Peters, Annette A1 - Postma, Dirkje S A1 - Pramstaller, Peter P A1 - Price, Jackie F A1 - Qi, Lu A1 - Olli T Raitakari A1 - Rankinen, Tuomo A1 - Rao, D C A1 - Rice, Treva K A1 - Ridker, Paul M A1 - Rioux, John D A1 - Ritchie, Marylyn D A1 - Rudan, Igor A1 - Veikko Salomaa A1 - Nilesh J Samani A1 - Saramies, Jouko A1 - Sarzynski, Mark A A1 - Schunkert, Heribert A1 - Schwarz, Peter E H A1 - Peter Sever A1 - Alan R Shuldiner A1 - Sinisalo, Juha A1 - Stolk, Ronald P A1 - Strauch, Konstantin A1 - Tönjes, Anke A1 - Trégouët, David-Alexandre A1 - Tremblay, Angelo A1 - Tremoli, Elena A1 - Virtamo, Jarmo A1 - Vohl, Marie-Claude A1 - Völker, Uwe A1 - Waeber, Gérard A1 - Gonneke Willemsen A1 - Witteman, Jacqueline C A1 - Zillikens, M Carola A1 - Adair, Linda S A1 - Amouyel, Philippe A1 - Asselbergs, Folkert W A1 - Assimes, Themistocles L A1 - Bochud, Murielle A1 - Boehm, Bernhard O A1 - Boerwinkle, Eric A1 - Bornstein, Stefan R A1 - Erwin P Bottinger A1 - Bouchard, Claude A1 - Cauchi, Stéphane A1 - Chambers, John C A1 - Chanock, Stephen J A1 - Cooper, Richard S A1 - de Bakker, Paul I W A1 - George Dedoussis A1 - Luigi Ferrucci A1 - Franks, Paul W A1 - Froguel, Philippe A1 - Leif C Groop A1 - Christopher A Haiman A1 - Hamsten, Anders A1 - Hui, Jennie A1 - Hunter, David J A1 - Hveem, Kristian A1 - Kaplan, Robert C A1 - Mika Kivimäki A1 - Kuh, Diana A1 - Laakso, Markku A1 - Yongmei Liu A1 - Nicholas G Martin A1 - März, Winfried A1 - Melbye, Mads A1 - Andres Metspalu A1 - Moebus, Susanne A1 - Munroe, Patricia B A1 - Njølstad, Inger A1 - Ben A Oostra A1 - Palmer, Colin N A A1 - Nancy L Pedersen A1 - Markus Perola A1 - Pérusse, Louis A1 - Peters, Ulrike A1 - Power, Chris A1 - Quertermous, Thomas A1 - Rauramaa, Rainer A1 - Fernando Rivadeneira A1 - Saaristo, Timo E A1 - Saleheen, Danish A1 - Sattar, Naveed A1 - Eric E Schadt A1 - Schlessinger, David A1 - Eline P Slagboom A1 - Snieder, Harold A1 - Timothy Spector A1 - Thorsteinsdottir, Unnur A1 - Stumvoll, Michael A1 - Tuomilehto, Jaakko A1 - André G Uitterlinden A1 - Uusitupa, Matti A1 - van der Harst, Pim A1 - Walker, Mark A1 - Wallaschofski, Henri A1 - Wareham, Nicholas J A1 - Watkins, Hugh A1 - David R Weir A1 - Wichmann, H-Erich A1 - James F Wilson A1 - Zanen, Pieter A1 - Ingrid B Borecki A1 - Deloukas, Panos A1 - Caroline S Fox A1 - Iris M Heid A1 - Jeff O'Connell A1 - David P Strachan A1 - Stefansson, Kari A1 - Cornelia M van Duijn A1 - Gonçalo R Abecasis A1 - Lude L Franke A1 - Timothy M Frayling A1 - McCarthy, Mark I A1 - Peter M Visscher A1 - Scherag, Andre A1 - Willer, Cristen J A1 - Boehnke, Michael A1 - Mohlke, Karen L A1 - Lindgren, Cecilia M A1 - Beckmann, Jacques S A1 - Barroso, Inês A1 - Kari E North A1 - Ingelsson, Erik A1 - Joel N Hirschhron A1 - Ruth J F Loos A1 - Elizabeth K Speliotes KW - Age Factors KW - BMI KW - Continental Population Groups KW - Energy Metabolism KW - Europe KW - Female KW - Genome-Wide Association Study KW - Glutamic Acid KW - Humans KW - Insulin KW - Male KW - Obesity KW - Polymorphism, Single Nucleotide KW - Quantitative Trait Loci KW - Synapses AB -

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

VL - 518 IS - 7538 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract ER - TY - JOUR T1 - Common genetic variants associated with cognitive performance identified using the proxy-phenotype method. JF - Proc Natl Acad Sci U S A Y1 - 2014 A1 - Cornelius A Rietveld A1 - Tõnu Esko A1 - Gail Davies A1 - Pers, Tune H A1 - Turley, Patrick A1 - Benyamin, Beben A1 - Chabris, Christopher F A1 - Emilsson, Valur A1 - Andrew D Johnson A1 - Lee, James J A1 - Christiaan de Leeuw A1 - Riccardo E Marioni A1 - Sarah E Medland A1 - Michael B Miller A1 - Rostapshova, Olga A1 - Sven J van der Lee A1 - Anna A E Vinkhuyzen A1 - Amin, Najaf A1 - Dalton C Conley A1 - Derringer, Jaime A1 - Cornelia M van Duijn A1 - Fehrmann, Rudolf A1 - Lude L Franke A1 - Edward L Glaeser A1 - Narelle K Hansell A1 - Caroline Hayward A1 - Iacono, William G A1 - Carla A Ibrahim-Verbaas A1 - Vincent Jaddoe A1 - Karjalainen, Juha A1 - David I Laibson A1 - Paul Lichtenstein A1 - David C Liewald A1 - Patrik K E Magnusson A1 - Nicholas G Martin A1 - McGue, Matt A1 - McMahon, George A1 - Nancy L Pedersen A1 - Pinker, Steven A1 - David J Porteous A1 - Posthuma, Danielle A1 - Fernando Rivadeneira A1 - Smith, Blair H A1 - John M Starr A1 - Henning Tiemeier A1 - Nicholas J Timpson A1 - Trzaskowski, Maciej A1 - André G Uitterlinden A1 - Verhulst, Frank C A1 - Mary E Ward A1 - Margaret J Wright A1 - George Davey Smith A1 - Ian J Deary A1 - Johannesson, Magnus A1 - Plomin, Robert A1 - Peter M Visscher A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger KW - Cell Adhesion Molecules, Neuronal KW - Cognition KW - Female KW - Humans KW - Learning KW - Male KW - Memory KW - Multifactorial Inheritance KW - Nerve Tissue Proteins KW - Neuronal Plasticity KW - Octamer Transcription Factors KW - Polymorphism, Single Nucleotide KW - Synaptic Transmission AB -

We identify common genetic variants associated with cognitive performance using a two-stage approach, which we call the proxy-phenotype method. First, we conduct a genome-wide association study of educational attainment in a large sample (n = 106,736), which produces a set of 69 education-associated SNPs. Second, using independent samples (n = 24,189), we measure the association of these education-associated SNPs with cognitive performance. Three SNPs (rs1487441, rs7923609, and rs2721173) are significantly associated with cognitive performance after correction for multiple hypothesis testing. In an independent sample of older Americans (n = 8,652), we also show that a polygenic score derived from the education-associated SNPs is associated with memory and absence of dementia. Convergent evidence from a set of bioinformatics analyses implicates four specific genes (KNCMA1, NRXN1, POU2F3, and SCRT). All of these genes are associated with a particular neurotransmitter pathway involved in synaptic plasticity, the main cellular mechanism for learning and memory.

VL - 111 IS - 38 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25201988?dopt=Abstract ER - TY - JOUR T1 - GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. JF - Science Y1 - 2013 A1 - Cornelius A Rietveld A1 - Sarah E Medland A1 - Derringer, Jaime A1 - Yang, Jian A1 - Tõnu Esko A1 - Martin, Nicolas W A1 - Westra, Harm-Jan A1 - Shakhbazov, Konstantin A1 - Abdel Abdellaoui A1 - Agrawal, Arpana A1 - Albrecht, Eva A1 - Alizadeh, Behrooz Z A1 - Amin, Najaf A1 - Barnard, John A1 - Baumeister, Sebastian E A1 - Benke, Kelly S A1 - Bielak, Lawrence F A1 - Boatman, Jeffrey A A1 - Patricia A. Boyle A1 - Gail Davies A1 - Christiaan de Leeuw A1 - Eklund, Niina A1 - Daniel S Evans A1 - Rudolf Ferhmann A1 - Fischer, Krista A1 - Gieger, Christian A1 - Gjessing, Håkon K A1 - Hägg, Sara A1 - Harris, Jennifer R A1 - Caroline Hayward A1 - Holzapfel, Christina A1 - Carla A Ibrahim-Verbaas A1 - Ingelsson, Erik A1 - Jacobsson, Bo A1 - Joshi, Peter K A1 - Jugessur, Astanand A1 - Marika A Kaakinen A1 - Kanoni, Stavroula A1 - Karjalainen, Juha A1 - Kolcic, Ivana A1 - Kristiansson, Kati A1 - Kutalik, Zoltán A1 - J. Lahti A1 - Lee, Sang H A1 - Lin, Peng A1 - Penelope A Lind A1 - Yongmei Liu A1 - Kurt Lohman A1 - Loitfelder, Marisa A1 - McMahon, George A1 - Vidal, Pedro Marques A1 - Osorio Meirelles A1 - Lili Milani A1 - Myhre, Ronny A1 - Nuotio, Marja-Liisa A1 - Christopher J Oldmeadow A1 - Katja E Petrovic A1 - Wouter J Peyrot A1 - Polasek, Ozren A1 - Quaye, Lydia A1 - Reinmaa, Eva A1 - Rice, John P A1 - Rizzi, Thais S A1 - Schmidt, Helena A1 - Schmidt, Reinhold A1 - Albert Vernon Smith A1 - Jennifer A Smith A1 - Toshiko Tanaka A1 - Antonio Terracciano A1 - van der Loos, Matthijs J H M A1 - Vitart, Veronique A1 - Völzke, Henry A1 - Jürgen Wellmann A1 - Lei Yu A1 - Wei Zhao A1 - Allik, Jüri A1 - John R. Attia A1 - Bandinelli, Stefania A1 - Bastardot, François A1 - Jonathan P. Beauchamp A1 - David A Bennett A1 - Klaus Berger A1 - Laura Bierut A1 - Dorret I Boomsma A1 - Bültmann, Ute A1 - Campbell, Harry A1 - Chabris, Christopher F A1 - Cherkas, Lynn A1 - Chung, Mina K A1 - Francesco Cucca A1 - de Andrade, Mariza A1 - Philip L de Jager A1 - De Neve, Jan-Emmanuel A1 - Ian J Deary A1 - George Dedoussis A1 - Deloukas, Panos A1 - Dimitriou, Maria A1 - Guðny Eiríksdóttir A1 - Elderson, Martin F A1 - Johan G Eriksson A1 - Jessica Faul A1 - Luigi Ferrucci A1 - Melissa E Garcia A1 - Grönberg, Henrik A1 - Guðnason, Vilmundur A1 - Hall, Per A1 - Harris, Juliette M A1 - Tamara B Harris A1 - Nicholas D Hastie A1 - Andrew C Heath A1 - Dena G Hernandez A1 - Hoffmann, Wolfgang A1 - Hofman, Adriaan A1 - Holle, Rolf A1 - Holliday, Elizabeth G A1 - Jouke-Jan Hottenga A1 - Iacono, William G A1 - Illig, Thomas A1 - Järvelin, Marjo-Riitta A1 - Kähönen, Mika A1 - Kaprio, Jaakko A1 - Kirkpatrick, Robert M A1 - Kowgier, Matthew A1 - Latvala, Antti A1 - Lenore J Launer A1 - Lawlor, Debbie A A1 - Lehtimäki, Terho A1 - Li, Jingmei A1 - Paul Lichtenstein A1 - Lichtner, Peter A1 - David C Liewald A1 - Pamela A F Madden A1 - Patrik K E Magnusson A1 - Mäkinen, Tomi E A1 - Masala, Marco A1 - McGue, Matt A1 - Andres Metspalu A1 - Mielck, Andreas A1 - Michael B Miller A1 - Grant W Montgomery A1 - Mukherjee, Sutapa A1 - Nyholt, Dale R A1 - Ben A Oostra A1 - Palmer, Lyle J A1 - Aarno Palotie A1 - Brenda W J H Penninx A1 - Markus Perola A1 - Peyser, Patricia A A1 - Preisig, Martin A1 - Katri Räikkönen A1 - Olli T Raitakari A1 - Realo, Anu A1 - Ring, Susan M A1 - Ripatti, Samuli A1 - Fernando Rivadeneira A1 - Rudan, Igor A1 - Rustichini, Aldo A1 - Veikko Salomaa A1 - Sarin, Antti-Pekka A1 - Schlessinger, David A1 - Rodney J Scott A1 - Snieder, Harold A1 - St Pourcain, Beate A1 - John M Starr A1 - Sul, Jae Hoon A1 - Surakka, Ida A1 - Svento, Rauli A1 - Teumer, Alexander A1 - Henning Tiemeier A1 - van Rooij, Frank J A A1 - Van Wagoner, David R A1 - Vartiainen, Erkki A1 - Viikari, Jorma A1 - Vollenweider, Peter A1 - Vonk, Judith M A1 - Waeber, Gérard A1 - David R Weir A1 - Wichmann, H-Erich A1 - Elisabeth Widen A1 - Gonneke Willemsen A1 - James F Wilson A1 - Alan F Wright A1 - Dalton C Conley A1 - Davey-Smith, George A1 - Lude L Franke A1 - Groenen, Patrick J F A1 - Hofman, Albert A1 - Johannesson, Magnus A1 - Sharon L R Kardia A1 - Krueger, Robert F A1 - David I Laibson A1 - Nicholas G Martin A1 - Meyer, Michelle N A1 - Posthuma, Danielle A1 - A. Roy Thurik A1 - Nicholas J Timpson A1 - André G Uitterlinden A1 - Cornelia M van Duijn A1 - Peter M Visscher A1 - Daniel J. Benjamin A1 - Cesarini, David A1 - Philipp D Koellinger KW - Cognition KW - Educational Status KW - Endophenotypes KW - Female KW - Genetic Loci KW - Genome-Wide Association Study KW - Humans KW - Male KW - Multifactorial Inheritance KW - Polymorphism, Single Nucleotide AB -

A genome-wide association study (GWAS) of educational attainment was conducted in a discovery sample of 101,069 individuals and a replication sample of 25,490. Three independent single-nucleotide polymorphisms (SNPs) are genome-wide significant (rs9320913, rs11584700, rs4851266), and all three replicate. Estimated effects sizes are small (coefficient of determination R(2) ≈ 0.02%), approximately 1 month of schooling per allele. A linear polygenic score from all measured SNPs accounts for ≈2% of the variance in both educational attainment and cognitive function. Genes in the region of the loci have previously been associated with health, cognitive, and central nervous system phenotypes, and bioinformatics analyses suggest the involvement of the anterior caudate nucleus. These findings provide promising candidate SNPs for follow-up work, and our effect size estimates can anchor power analyses in social-science genetics.

VL - 340 IS - 6139 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23722424?dopt=Abstract ER -